Open Exchangehttp://blog.assaydepot.com
an Assay Depot BlogWed, 05 Nov 2014 20:06:47 +0000en-UShourly1http://wordpress.org/?v=4.2.3Precompetitive Collaboration: Emerging Realism in the Pharma Worldhttp://blog.assaydepot.com/2014/11/precompetitive-collaboration-emerging-realism-pharma-world-2/
http://blog.assaydepot.com/2014/11/precompetitive-collaboration-emerging-realism-pharma-world-2/#commentsWed, 05 Nov 2014 16:01:22 +0000http://blog.assaydepot.com/?p=3981In the world of drug discovery, pharmaceutical companies face a very sobering statistic – more than 90% of the drugs that reach clinical testing will fail. This high failure rate is not only a major financial concern for the pharma industry, but it also negatively affects the millions of patients that are sick and desperately […]

]]>In the world of drug discovery, pharmaceutical companies face a very sobering statistic – more than 90% of the drugs that reach clinical testing will fail. This high failure rate is not only a major financial concern for the pharma industry, but it also negatively affects the millions of patients that are sick and desperately waiting for new medicines. Reducing the clinical failure rate is a critical step in creating a more successful and sustainable pharmaceutical industry.

Researchers in pharma/biotech and academia faced a similar challenge during the late 1980s and early 1990s with AIDS/HIV. At that time, the scientific community was able to rapidly and successfully develop several anti-HIV drugs thanks, in no small part, to the use of pre-competitive research collaborations. Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA), writes, “precompetitive research is a subset of translational research that focuses on improving the tools and techniques needed for successful translation, and not on development of a specific product.”

In a precompetitive collaboration, a variety of different organizations (that typically would compete with each other) work together or share information. For AIDS/HIV research, partners that worked together precompetitively included pharmaceutical and biotech companies, academic research centers and government research institutes.

Pharmaceutical companies have historically done all of their drug discovery research in house. But in the last 10 years, it has become increasingly clear that the pharmaceutical industry must change its research model if it is to remain viable. Challenges facing the industry include:

Increasing cost of research coupled with abysmal rates of clinical success

Expiration of patent protection leading to loss of exclusivity (the so-called patent cliff)

Competition from biosimilars and generics

To address these challenges, some pharmaceutical companies are, for the first time, engaging in precompetitive partnerships with other pharma competitors, with government organizations and with academic research centers. For example, the large pharma company GlaxoSmithKline recently formed a precompetitive collaboration with the Wellcome Trust Sanger Institute and the European Bioinformatics Institute to establish the Center for Therapeutic Target Validation (CTTV). The three organizations will pool resources to discover new potential drug targets that all of the partners will be able to access.

Additional precompetitive partnership examples include the Innovative Medicines Initiative (IMI) in Europe, the Critical Path Institute (CPI) in the US, the Structural Genomics Consortium (SGC) and Oxford University’s Target Discovery Institute (TDI). These partnerships are specifically geared toward translational research that will lead ultimately to the commercialization of new medicines.

Pharmaceutical companies and other large research organizations are beginning to work together precompetitively in other ways as well. Pfizer, AstraZeneca, the US National Cancer Institute and a host of other biotech, pharma and academic organizations have worked together with Assay Depot to create preclinical research marketplaces that share precompetitive information. Each Assay Depot client has its own private research marketplace but the underlying supplier and service databases are shared precompetitively. In 2015, some of the pharma companies will begin sharing supplier ratings as well.

Precompetitive research partnerships can, at times, be difficult to manage owing to the size and bureaucratic nature of large research partners. At times there are also legal challenges involving intellectual property rights that are often difficult to overcome. Nevertheless, the pooling of resources early in the drug discovery process, before a drug candidate has been selected for the clinic, should have an outsized effect on pharma productivity, leading to both increased innovation and reduced costs.

That said, it is important to understand that the time to act and establish precompetitive collaboration is now; as Janet Woodcock says in her article, “(T)he success of the drug development enterprise over the next decade may be at stake.”

]]>http://blog.assaydepot.com/2014/11/precompetitive-collaboration-emerging-realism-pharma-world-2/feed/3Starting a Conversation on Drug Discovery Biaseshttp://blog.assaydepot.com/2014/09/starting-conversation-drug-discovery-biases/
http://blog.assaydepot.com/2014/09/starting-conversation-drug-discovery-biases/#commentsTue, 23 Sep 2014 20:40:44 +0000http://blog.assaydepot.com/?p=3968From the desk of Chris Lipinski, PhD I’ve been thinking a lot lately about how to optimize for ligand affinity. Of course, this is a central theme of all drug discovery projects. At its core is the question of how physical and chemical relationships guide the interplay between the ligand, the protein target, and the […]

I’ve been thinking a lot lately about how to optimize for ligand affinity. Of course, this is a central theme of all drug discovery projects. At its core is the question of how physical and chemical relationships guide the interplay between the ligand, the protein target, and the water solvent. Existing measurements and techniques can directly reveal entropic and enthalpic contributions to this process, and ligand efficiency type of calculations can indirectly give similar information. In a somewhat convoluted process, after speaking at a Collaborative Drug Discovery (CDD) meeting in April, I began to think about how structure-based as opposed to high throughput screening (HTS) approaches might bias the compounds we develop, and how we might take advantage of those biases.

I’d like to start a larger conversation amongst drug discovery scientists to address these issues. To this end, I will be leading a live webinar event hosted by CDD, to begin to explore questions about whether the choice of the techniques that guide small molecule discovery efforts result in a systematic bias in the kinds of chemical leads we discover. We will discuss the benefits of different techniques and metrics, and especially as they relate to the differing goals in chemical biology and drug discovery. My hope is that if the webinar is provocative enough it might elicit listener ideas and help pull together some new insights in the broad drug discovery community. Please join me for what is sure to be a stimulating discussion.

]]>http://blog.assaydepot.com/2014/09/starting-conversation-drug-discovery-biases/feed/0Protocols.io: Crowdsourcing Scientific Protocolshttp://blog.assaydepot.com/2014/09/protocols-io-crowdsourcing-scientific-protocols/
http://blog.assaydepot.com/2014/09/protocols-io-crowdsourcing-scientific-protocols/#commentsMon, 08 Sep 2014 18:09:44 +0000http://blog.assaydepot.com/?p=3346Anyone who has taken a general laboratory class knows that the lab manual has multiple protocols that one follows in order to complete each week’s assignment. However, while the class laboratory protocol has been thoroughly tested, academic and industry protocols are often changed and improved as new information is gleaned from previous experiments. A new […]

Through crowdsourcing, Protocols.io can provide up-to-date corrections for scientific research protocols.1

Anyone who has taken a general laboratory class knows that the lab manual has multiple protocols that one follows in order to complete each week’s assignment. However, while the class laboratory protocol has been thoroughly tested, academic and industry protocols are often changed and improved as new information is gleaned from previous experiments. A new method can be found to improve the purity and yield of a protein purification, or the incubation time of a transformation is discovered to be optimal at room temperature rather than 42o C. While these types of changes can be tracked within a single lab, protocol changes are usually not noted by the general scientific community until the project is published, which can take many years. ZappyLab, a start up that is dedicated to creating science apps for research and benchwork, has created Protocols.io (beta) in order to remedy this issue. Protocols.io requires crowdsourcing for its success as an up-to-date protocol repository.

Crowdsourcing, or the practice of using data and information from a large number of people, has become increasingly popular with technological advances. The internet and smartphones have globalized information and increased connectivity. Websites such as Wikipedia rely on crowdsourcing for the content generation and the content validation. Scientists should be able to take advantage of crowdsourcing and the increase in information connectivity in conducting effective research.

Projects such as Protocols.io or Experiment.com are examples of the new exciting ways that research is improving, whether through crowdsourcing protocols and increasing protocol accessibility or through crowdfunding of scientific research. While software companies and tech companies such as Mathworks and R have been using crowdsourcing as a way to fix bugs and glitches, biotech companies have only recently used crowdsourcing as a way to improve research methods. After all, the ubiquitous presence of smartphones, tablets, and laptops has increased connectivity, and the scientific community can utilize this increased connectivity to promote and improve research. We at Assay Depot have been an advocate of such connectivity in scientific research, through our free platform to connect scientists to over 10,000 vendor services. However, despite the promise of drastically improving the quality of bench research time, ZappyLab acknowledges that the building of a crowd large enough is the biggest challenge for Protocols’ success, especially as scientists may not think of using an app for their research. ZappyLab has been focused on building their user acquisition for their other science applications and hopes that many current ZappyLab users will continue to use and crowdsource Protocols.

Imagine how much wasted time researchers can save if they are able to connect to an up-to-date protocol. One scientist might spend months optimizing a protocol, and now there is a tool where he can share his insights and potentially save another scientist the wasted months. ZappyLab’s Protocols can become a great resource and benefit all research scientists, as the time will be spent on real breakthroughs rather than re-discovering something that someone else already optimized or discovered. This is one app that the scientific research community should keep an eye on, especially as improvements to research efficiency can promote real discoveries.

]]>http://blog.assaydepot.com/2014/09/protocols-io-crowdsourcing-scientific-protocols/feed/0Drug Discovery Collapse: How to Fix Irreproducible Research?http://blog.assaydepot.com/2014/08/drug-discovery-collapse-irreproducible-research/
http://blog.assaydepot.com/2014/08/drug-discovery-collapse-irreproducible-research/#commentsMon, 25 Aug 2014 17:36:47 +0000http://blog.assaydepot.com/?p=3605Drug discovery, ever a challenge, can be likened to a tall structure. The upper stories rely on the stability of the floors below it, and a solid foundation is a must. No lofty heights will be reached when the base is not secure. And so, it is not a surprise that a drug discovery project […]

A large structure can’t stand without a solid base. It’s the same with drug discovery and irreproducible research. Image credit: Wikimedia Commons

Drug discovery, ever a challenge, can be likened to a tall structure. The upper stories rely on the stability of the floors below it, and a solid foundation is a must. No lofty heights will be reached when the base is not secure.

And so, it is not a surprise that a drug discovery project will collapse if its own base is, well, baseless. Unfortunately, this is not just a hypothetical scenario: There is an increasing realization that many published early stage investigations cannot be repeated and causing the rise of irreproducible research. In one study that underscores the extent of the problem, scientists at Amgen attempted to reproduce the findings of fifty-three “landmark” articles – and only succeeded with six.[1]

What gives? Although it happens too often that a so-called research “finding” in fact stemmed from fraud, it is more often the case that irreproducible research results are caused by rushed, less-than-careful work by scientists under extreme pressure to publish, particularly due to funding and job security concerns. With a weak job market and tightened federal budgets, the pressure has been especially intense. Wait too long to announce results, and another group might reach the finish line first and “scoop” a project. In such an environment, researchers may pay less heed to internal doubts that call for further experiments. As Richard Feynman said, “The first principle is that you must not fool yourself, and you are the easiest person to fool.”

And even when an experiment is performed meticulously, crucial details might be left out of the manuscript. An experiment might only work in a narrow range of temperatures, for example, and others trying to repeat the experiment could flounder without this information. The writers of the original report may feel that there is not enough room in an article to list all the details, or, more nefariously, they don’t want competitors to learn the secrets to their success, and thus continuing the chain of irreproducible research.

Alarm bells are ringing. Nature – one of those top-tier journals that scientists break their backs to get into – wrote about the problem of irreproducible research in a series of articles.[2] Many concerned writers have weighed in about what to do. Although there are disagreements, one common theme emerges: transparency.

Many in the scientific community feel that journals should insist that authors provide every relevant experimental detail in a manuscript. A slight detail can mean a world of difference. Both positive and negative data should be reported, rather than trying to present a finding in the most exciting way possible. Some in the community have even suggested that at least part of the peer review process should be open to the readership. With questionable studies making it through peer review, it has been wondered if the quality of peer review suffers from its secrecy.

People in a position to award grants, tenure, promotions, and job offers can help by looking beyond an applicant’s number of publications in high-impact journals. What is the real quality of the research? After all, irreproducible research is not quality research. And those performing the research should remember that they are less likely to avoid embarrassing corrections and retractions if their experiments are well-rounded. Dedicated service providers through Assay Depot are available to assist. Irreproducibility in research has many causes and no simple answer, but making repairs is imperative. Drug discovery depends on it.

]]>http://blog.assaydepot.com/2014/08/drug-discovery-collapse-irreproducible-research/feed/1Innovation Goes Front and Center in Drug Discoveryhttp://blog.assaydepot.com/2014/08/innovation-and-drug-discovery/
http://blog.assaydepot.com/2014/08/innovation-and-drug-discovery/#commentsThu, 14 Aug 2014 20:06:12 +0000http://blog.assaydepot.com/?p=3750“Innovation” is suddenly the word on everybody’s lips. Pfizer launched “Centers for Therapeutic Innovation”, Johnson and Johnson followed with their “Innovation Centres” and now Merck followed with their “Innovation hubs”. In fact, it happened so fast that many of us in the dusty halls of academia are still trying to get a grip on what’s […]

]]>“Innovation” is suddenly the word on everybody’s lips. Pfizer launched “Centers for Therapeutic Innovation”, Johnson and Johnson followed with their “Innovation Centres” and now Merck followed with their “Innovation hubs”. In fact, it happened so fast that many of us in the dusty halls of academia are still trying to get a grip on what’s going on. We got a view point from Dr. Andrew Johnson of the University of California and it seems like these things are innovative in more ways than one. Here’s a blog explaining what all this “innovation” is about.

Innovation is the way forward for drug discovery and academic science. Image from www.european-coatings.com

The first thing you should know is that Innovation Centers are born out of necessity. Patents are expiring on these drug company’s main earners while research and development costs have spiraled out of control. Yet these companies still need to find new targets to develop into more life-saving, money-earning therapeutics. Innovation Centers represent a radical shift in strategy that drug companies hope will allow them to deliver more while risking less.

The model goes something like this. If the Innovation Center thinks the idea is a good one which has genuine potential to become a drug then, in principle, they are ‘in’. As a friend in London described it, “it’s almost “Britain’s Got Talent” for scientists. The details vary from company to company and project to project, but the stated intention is to take early stage projects as well as compounds closer to the clinic and thus create an externalised pipeline. From that point the model is exciting in its flexibility with the company aiming to provide expertise uniquely targeted to the demands of the project. In doing this, web-based platforms, such as Assay Depot, play a critical role. Assay Depot enables rapid, cost-effective access to an exhaustive array of dedicated research services, technical experts and CROs, a vital requirement in a business where in house R&D is replaced with “on demand” activity. For example, an innovation partnership might access lab space in an incubator, such as in “Biotech and Beyond” founded by Assay Depot CEO Kevin Lustig, or rapidly outsource aspects of drug development (such as DMPK, Pharmacology, medicinal chemistry etc) that would be beyond the scope of the average academic. The critical part of the innovation model is that the ties in this partnership are weak and flexible. The drug company can get in quick on a new target and get out just as fast if the target proves to be a dud.

What this means for the researcher on the bench and ultimately what it will mean for drug discovery are still open-ended ideas. In theory Innovation Centers offer a much needed new source of funding and know-how for applied science as well as an entrepreneurial career route distinct from academia. On the other hand the locations of these centers (San Francisco, Boston, New York and London) is currently not very innovative and so surely casting a wider net and preventing competition for the same targets will require the geographical expansion of the centers, to include China and India for example. In the end proof of lasting success of these Innovation Centers will be measured in the number and value of new products brought to the healthcare market.

]]>http://blog.assaydepot.com/2014/08/innovation-and-drug-discovery/feed/0Children With a Rare Disease May Hold a Key to New Antiviralshttp://blog.assaydepot.com/2014/08/children-rare-disease-may-hold-clues-new-antivirals/
http://blog.assaydepot.com/2014/08/children-rare-disease-may-hold-clues-new-antivirals/#commentsMon, 04 Aug 2014 16:52:21 +0000http://blog.assaydepot.com/?p=3737Sometimes, in tragic circumstances, a lesson can be learned and applied in unexpected ways. That appears to be the case with a rare disease that produces debilitating symptoms in children – but might also offer clues to developing a new class of antivirals. The particular disease, an extremely rare congenital disorder called CDG-IIb, affects the […]

]]>Sometimes, in tragic circumstances, a lesson can be learned and applied in unexpected ways. That appears to be the case with a rare disease that produces debilitating symptoms in children – but might also offer clues to developing a new class of antivirals.

The particular disease, an extremely rare congenital disorder called CDG-IIb, affects the processing of proteins. Most proteins are glycosylated, that is, modified by the addition of sugars or chains of sugars, which is important for proper function. In patients with a CDG-IIb, an enzyme that is partly responsible for glycosylation is defective. Unfortunately, patients suffer from a multitude of problems, including neurological defects, bone fractures, and hearing loss.

Research into rare diseases has grown substantially in the last 30 years, and there are many avenues through which people can contribute to help those afflicted. In this instance there was an apparent additional benefit to studying CDG-IIb.

That’s because this disorder, although causing deficiencies in the immune system on top of all the other troubles, did not bring about an especially high number of infections in two young siblings who have CDG-IIb. A team of researchers set out to make sense of this puzzle.[1]

The answer, it turns out, is that many viruses, including HIV and the hepatitis C virus, need glycosylated proteins themselves for their outer coat, our glycosylated proteins. Viruses, after all, use our machinery and cellular components to build copies of themselves in order to spread and multiply. Indeed, cells from the siblings in the study resisted infection from such viruses.

The search for new and improved antivirals is a vibrant field, as reflected by the number of service providers offering antiviral testing through Assay Depot. But one might think: How could this rare disease be useful for antivirals if glycosylation is so crucial? Timing may be the solution. There is the possibility that, by blocking this glycosylation step just temporarily, viruses will sputter out while the person remains unscathed. Scientists in fact have been working on inhibitors of this type for two decades.[2] One is already on the market for another disorder, with only mild side effects.

These findings underscore that studying rare diseases is valuable not just for helping the relatively few who are affected. Learning about the underlying biology may reveal insights important for some of the most common ailments in the world.

]]>http://blog.assaydepot.com/2014/08/children-rare-disease-may-hold-clues-new-antivirals/feed/0Crowdfunding of an HIV Vaccine Brings Hope and Skepticismhttp://blog.assaydepot.com/2014/07/crowdfunding-hiv-vaccine-brings-hope-skepticism/
http://blog.assaydepot.com/2014/07/crowdfunding-hiv-vaccine-brings-hope-skepticism/#commentsMon, 28 Jul 2014 19:28:39 +0000http://blog.assaydepot.com/?p=3393We have recently discussed here how crowdfunding — donations from the general public in support of a cause, idea, or invention — has caught the attention of scientists seeking financial backing in an era of tight budgets. The brave new world of crowdfunding in science raises questions that defy easy answers. What is essential to […]

Can HIV be “controlled” by a vaccine? That’s the hope of one nonprofit organization, who successfully raised crowdfunding cash. Image credit: Wikimedia Commons.

We have recently discussed here how crowdfunding — donations from the general public in support of a cause, idea, or invention — has caught the attention of scientists seeking financial backing in an era of tight budgets. The brave new world of crowdfunding in science raises questions that defy easy answers. What is essential to lead a successful crowdfunding campaign? Is it possible to win the hearts and minds of laypeople AND impress one’s scientific peers?

A case in point is the recent crowdfunding campaign by the nonprofit corporation Immunity Project. The organization has noted that about 1 out of 300 people are HIV “controllers”, meaning that, although they might wind up with a low level of HIV, the virus may be kept in check. The Immunity Project hopes to come out with a vaccine that would endow everyone with the same immunity enjoyed by the controllers. The organization hopes to have a vaccine ready in 2016, and it would be provided at no charge. The money it sought was for a final experiment before Phase I clinical testing.

Some of the reaction from the scientific community, however, has been more than a little critical:

“The concept they’re selling is an old concept that has been shown not to work, and it can’t work.”[1]

“It seems like they’re going straight to the public and making appeals to emotion because they don’t have the scientific background to establish themselves in the research community.”[1]

One point that has raised a number of eyebrows is the lack of publications that support the organization’s approach. CEO Reid Rubsamen has reported that an article has been submitted to a peer-reviewed journal. Rubsamen was the host of an “Ask Me Anything” segment on the social networking service Reddit. Hundreds of comments and questions poured in. Some people expressed doubts and concerns. But many others articulated their enthusiasm, even if they were not experts themselves:

“I donated. I have no idea if what you’re doing is feasible or not, but it looks to me like you’re taking a brand new (or at least uncommon) approach to medical research, and that excites me.”[2]

A few held contempt for established institutions and commended Immunity Project’s undertaking as a humanitarian alternative:

“It restores some of my faith in humanity knowing that there are people like you out there. Pharmaceutical companies are among the most evil corporations out there. Where they are looking for a vaccine only to provide to the wealthiest of nations and make billions in profits, your team is trying to actually provide a service to humanity.”[2]

In Reddit and elsewhere, there have been enough fans that Immunity Project was able to meet its crowdfunding goal of $462,000. (Four people individually donated $50,000.) This amount is not particularly a king’s ransom in science dollars, and the group has needed to make every dollar count, including finding a discounted flow cytometer. (Flow cytometry, with many vendors offering their services through Assay Depot, is widely applied to vaccine research.)

Regardless of whether Immunity Project succeeds or not, it is the nature of research that many, if not most, scientific projects supported by crowdfunding will not pan out. Will that mean that supporters will grow disillusioned and snap their wallets shut? Or is the excitement of backing a venture at the edge of knowledge enough for donors to come back again and again? This is one experiment whose results are not yet in.

]]>http://blog.assaydepot.com/2014/07/crowdfunding-hiv-vaccine-brings-hope-skepticism/feed/0World’s First Academic Life Science Research Exchangehttp://blog.assaydepot.com/2014/07/worlds-first-academic-life-science-research-exchange-3/
http://blog.assaydepot.com/2014/07/worlds-first-academic-life-science-research-exchange-3/#commentsWed, 23 Jul 2014 18:39:34 +0000http://blog.assaydepot.com/?p=3946Connecting academic scientists to the global life science ecosystem Like everyone else, academic researchers are finding that funding sources are drying up and that they somehow must do more research work with less money. To do something about it, a group of Universities in Missouri and Kansas have teamed up with Assay Depot to create […]

]]>Connecting academic scientists to the global life science ecosystem

Like everyone else, academic researchers are finding that funding sources are drying up and that they somehow must do more research work with less money. To do something about it, a group of Universities in Missouri and Kansas have teamed up with Assay Depot to create the world’s first academic Research Exchange. Created in collaboration with the Kansas City Area Life Sciences Institute, the University of Missouri, the University of Kansas and Kansas State University, this science marketplace facilitates research collaboration and cooperation across the Midwest and allows researchers to access potential research partners in over 100 countries.

Assay Depot partners with Kansas City Area Life Science Institute to create world’s first academic research exchange

In effect it gives all academic researchers access to the tools and technologies that have historically been restricted to well-funded pharmaceutical laboratories. Our hope of course is that easy access to experts and tools will allow every academic researcher to engage in translational research, cross the so-called “valley of death” and find a partner with the resources needed to develop and commercialize a new potentially life-saving therapy. But we’d be happy if the platform simply helped thousands of outstanding Midwest scientists take the next step in their research projects and life’s work.

The underlying purpose behind the creation of the platform is to make the unknown known in the field of Life Sciences – to bring the information scientists are looking for to their doorstep rather than making them search for it. By empowering researchers with the information and tools they need to create and run any life science research project, researchers become limited only by their imagination (and funding) in what they can achieve.

Assay Depot has created similar private Research Exchanges (aka Innovation Marketplaces) for four of the world’s top ten pharmaceutical companies, including Pfizer and AstraZeneca, and the National Cancer Institute (NCI). In this world of shrinking research budgets, even the world’s largest research organizations need ways to save time and money and access the innovation in the long tail of global CROs.

]]>http://blog.assaydepot.com/2014/07/worlds-first-academic-life-science-research-exchange-3/feed/0CRISPR Marches Forward: Correcting a Disease in Animalshttp://blog.assaydepot.com/2014/07/crispr-marches-forward/
http://blog.assaydepot.com/2014/07/crispr-marches-forward/#commentsMon, 14 Jul 2014 21:26:10 +0000http://blog.assaydepot.com/?p=3571As we previously discussed, CRISPR-mania is sweeping the globe. (Okay, it might not be as big as Beatlemania, but more than a few life science researchers have probably squealed in delight.) The CRISPR system, derived from bacteria’s fight against viruses and tailored so that it can snip away genetic material in other organisms, has generated […]

]]>As we previously discussed, CRISPR-mania is sweeping the globe. (Okay, it might not be as big as Beatlemania, but more than a few life science researchers have probably squealed in delight.) The CRISPR system, derived from bacteria’s fight against viruses and tailored so that it can snip away genetic material in other organisms, has generated considerable excitement for its potential use as a type of molecular surgeon, cutting away harmful genes that lead to human disease. Companies in the know about CRISPR are providing their services through Assay Depot.

Although not ready for humans just yet, the CRISPR system was used to oppose the effects of a disease in mice. Image credit: Wikimedia Commons

Now, scientists have used methodology based on CRISPR to target a genetic disease.[1] They were interested in a rare human condition known as hereditary tyrosinemia type I (HTI), in which the body cannot completely break down the amino acid tyrosine, leading to severe liver damage that proves fatal. Lab mice are available that harbor the same genetic mutation which is harmful to mice and men alike. Treatments are available for human HTI, so pursuing the disease in mice through a CRISPR system was presented as a proof-of-principle. The researchers administered a DNA-chopping protein that is associated with CRISPR (Cas9), as well as a “guide” RNA to lead the protein to the right place in the mouse genome. They also introduced a stretch of non-defective DNA. That way, when the mice DNA is broken by Cas9, the natural repair system is able to sew in the correct sequence. Mice receiving one type of CRISPR package did not experience the swift weight loss observed with this disorder. Their livers had extensive patches of healthy cells, and markers of liver damage were greatly reduced, compared with controls.

Interestingly, a correction rate of only about 1/250 cells was determined, but liver cells with the healthy gene can repopulate the organ.[2] No off-target effects were found. Studying the transcription of the gene showed that, indeed, the modified RNA was transcribed. Some developments are needed before an approach like this could be available for humans. For one, the CRISPR treatment was delivered to the liver by hydrodynamic injection, a rapid administration of the material in a large volume of solution. This fast and furious injection would be dangerous for human patients, and a suitable alternative would need to be discovered. What’s more, many diseases may not be cured if only 1/250 cells are positively affected. However, these challenges have not dampened researchers’ excitement, where the hope that one day, CRISPR-based systems will be a solution to the tricky problem of mending troubled genes.

]]>http://blog.assaydepot.com/2014/07/crispr-marches-forward/feed/0Why Do Powerful Cancer Drugs Fail?http://blog.assaydepot.com/2014/07/powerful-anti-cancer-drugs-fail/
http://blog.assaydepot.com/2014/07/powerful-anti-cancer-drugs-fail/#commentsMon, 07 Jul 2014 20:52:42 +0000http://blog.assaydepot.com/?p=3937It’s a sad story that everyone is familiar with: A patient takes one or more well-known cancer drugs, and they work — for a while. However, after the respite, the cancer comes roaring back, this time impervious to the once powerful effects of the cancer drugs. Many people would view the disease’s return with resignation […]

It’s a sad story that everyone is familiar with: A patient takes one or more well-known cancer drugs, and they work — for a while. However, after the respite, the cancer comes roaring back, this time impervious to the once powerful effects of the cancer drugs. Many people would view the disease’s return with resignation and hope that some other intervention can help.

But does it have to be this way? Instead of waving the white flag, it might pay to examine how the cancer was able to resist treatment. That might be knowledge used to allow the cancer drugs to keep fighting.

Such is the focus of research by Dr. Robert Ladner, a professor at the University of Southern California (USC). Dr. Ladner and co-workers are interested in the widely used agent 5-fluorouracil (5-FU). This drug leads to the blockage of the natural conversion of deoxyuridine monophosphate (dUMP) in the body to deoxythymidine monophosphate (dTMP). As a result, dUMP builds up. One reason 5-FU is bad news for rapidly dividing, DNA-hungry cancer cells is that dUMP is enzymatically converted to deoxyuridine triphosphate (dUTP), which is “mistakenly” taken up into DNA, causing damage.[1]

Dr. Ladner and colleagues set out to help shed light on why, exactly, cancer cells develop resistance to 5-FU. They found that resistance to 5-FU in cancer cells correlates with increased production of the enzyme dUTPase, which converts dUTP back to dUMP. In other words, before dUTP can enter into DNA and throw a wrench into the works, resistant cancer cells knock it back down to dUMP.

Rather than just being a point of interest, the discovery of the role of dUTPase in resistance may highlight how it might be possible to prevent malignant cells from circumventing the effects of cancer drugs. In the case of 5-FU, Dr. Ladner and co-workers are developing ways to inhibit dUTPase. Dr. Ladner’s research has recently been supported by a donation of $500,000 from the Moore for Kids Foundation.[2,3]

Although the development of new cancer drugs is vital, there is hope, thanks to work like this at USC, that the old standbys can be assisted so that they can continue to attack this disease, even in the face of resistance. Researchers who are part of the battle and are interested in outsourcing oncology are welcome to explore the oncology resources available from Assay Depot. Fight on!